To realize the benefits of HIV care requires high medication adherence that has been found lower than previously assumed and declining over time in sub-Saharan Africa (SSA). Youths with still developing emotional and cognitive capacities face special and unique challenges to adherence. Despite a wealth of interventions designed to increase adherence outcomes, few have focused on the period of adolescence. Developing ways to increase adherence rates among adolescents is particularly important as this group experiences the fastest growth in new HIV/AIDS cases. Such interventions are important in resource-limited settings important where second-line therapy is often too expensive or altogether unavailable. Similarly, youths are often on pre-ART co-trimoxazole prophylaxis to defer the need to take costly ART, yet most interventions do not take this reality into account. The recent rapid rise in mobile phone coverage and ownership among developing country populations has spawned the advent of mobile-phone based interventions to improve health service delivery; short message service (SMS)-based interventions have been found to increase adherence rates to ART among adult patients, yet their effectiveness among an adolescent population remains unknown. Such interventions are likely particularly effective for adolescents who have been central to the rapid growth in mobile phone ownership in developing countries. This proposal suggests to develop and test potentially cost-effective and scalable short message service (SMS)-based interventions to improve adherence to ART and pre-ART prophylaxis, as well as retention in care among HIV positive young patients aged 15-24 at two clinics in Uganda. The first aim is to hold focus groups with key stakeholders to tailor the SMS-intervention to the local needs of youths. The second aim proposed is a two-year randomized controlled trial testing one- way and two-way SMS messages (the latter offer the possibility for clients to signal health problems for follow-up by clinic staff) against a control condition of usual care to determine which method of reminding and motivating drug adherence can best achieve its goals, and whether the potentially higher adherence achieved in the two-way messages justify their increased cost. The third aim is to synthesize lessons learned and discuss them with the clinics and other key stakeholders. A cost-effectiveness analysis of one- versus two-way messages will also be performed as part of this aim.